Summary of Study ST002203
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001406. The data can be accessed directly via it's Project DOI: 10.21228/M80421 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002203 |
| Study Title | Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma |
| Study Summary | Abstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting. |
| Institute | Brigham and Women's Hospital |
| Department | Department of Neurosurgery |
| Laboratory | Nathalie Y.R. Agar |
| Last Name | Stopka |
| First Name | Sylwia |
| Address | 60 Fenwood Rd |
| sstopka@bwh.harvard.edu | |
| Phone | 617-525-9746 |
| Submit Date | 2022-06-27 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | imzML |
| Analysis Type Detail | MALDI-MS |
| Release Date | 2022-07-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001406 |
| Project DOI: | doi: 10.21228/M80421 |
| Project Title: | Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma |
| Project Type: | Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma |
| Project Summary: | Abstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting. |
| Institute: | Brigham and Women's Hospital |
| Department: | Department of Neurosurgery |
| Laboratory: | Nathalie Y.R. Agar |
| Last Name: | Stopka |
| First Name: | Sylwia |
| Address: | 60 Fenwood Rd, |
| Email: | sstopka@bwh.harvard.edu |
| Phone: | 617-525-9746 |
Subject:
| Subject ID: | SU002289 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | sample_id |
|---|---|---|
| SA211360 | mouse_CD73 | Dataset1 |
| SA211361 | human_tumor_CD73 | Dataset2 |
| Showing results 1 to 2 of 2 |
Collection:
| Collection ID: | CO002282 |
| Collection Summary: | As stated in the manuscript Frozen resection tissue from 9 glioblastomas, including 4 cases with high CD73 and 5 cases with low CD73 by IHC, were selected for MALDI MSI. |
| Sample Type: | Brain |
Treatment:
| Treatment ID: | TR002301 |
| Treatment Summary: | N/A |
Sample Preparation:
| Sampleprep ID: | SP002295 |
| Sampleprep Summary: | As stated in the manuscript Frozen resection tissue from 9 glioblastomas, including 4 cases with high CD73 and 5 cases with low CD73 by IHC, were selected for MALDI MSI. Tissue was sectioned to 10 µm, thaw mounted onto indium-tin-oxide (ITO) slides, and serial sections were obtained for H&E staining. A high-resolution image of the whole H&E tissues was obtained through image stitching (Zeiss Observer Z.1, Oberkochen, Germany) using a plan-apochromat lens (20×) using an AxioCam MR3 camera. Matrix preparation of 1,5-diaminonaphthalene hydrochloride was prepared to a concentration of 4.3 mg/mL in 4.5/5/0.5 HPLC grade water/ethanol/1 M HCl (v/v/v). The matrix was sprayed using a TM-sprayer (HTX imaging, Carrboro, NC) with parameters of a flow rate (0.09 mL/min), spray nozzle velocity (1200 mm/min), spray nozzle temperature (75°C), nitrogen gas pressure (10 psi), track spacing (2 mm) and a four pass spray. |
Combined analysis:
| Analysis ID | AN003606 |
|---|---|
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | Bruker |
| Column | none |
| MS Type | MALDI |
| MS instrument type | FT-ICR |
| MS instrument name | Bruker Solarix FT-ICR-MS |
| Ion Mode | NEGATIVE |
| Units | Da |
Chromatography:
| Chromatography ID: | CH002665 |
| Instrument Name: | Bruker |
| Column Name: | none |
| Chromatography Type: | None (Direct infusion) |
MS:
| MS ID: | MS003360 |
| Analysis ID: | AN003606 |
| Instrument Name: | Bruker Solarix FT-ICR-MS |
| Instrument Type: | FT-ICR |
| MS Type: | MALDI |
| MS Comments: | Bruker software |
| Ion Mode: | NEGATIVE |
